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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2418-2424. Prepublished online as a Blood First Edition Paper on June 17, 2004; DOI 10.1182/blood-2004-04-1294. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1294v1 104/8/2418    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mirandola, P. Articles by Vitale, M. Search for Related Content PubMed PubMed Citation Articles by Mirandola, P. Articles by Vitale, M. Related Collections Immunobiology Apoptosis Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activated human NK and CD8+ T cells express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL-mediated cytotoxicity Prisco Mirandola, Cristina Ponti, Giuliana Gobbi, Ivonne Sponzilli, Mauro Vaccarezza, Lucio Cocco, Giorgio Zauli, Paola Secchiero, Francesco Antonio Manzoli, and Marco Vitale From the Department of Anatomy, Pharmacology, and Forensic Medicine, Human Anatomy Section, University of Parma, Italy; the Department of Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, Italy; the Department of Normal Human Morphology, University of Trieste, Italy; the Department of Morphology and Embriology, Human Anatomy Section, University of Ferrara, Italy; and the Istituto per i Trapianti d'organo e Immunocitologia-Consiglio Nazionale delle Ricerche, Bologna Unit, Research Institute "Codivilla-Putti," Istituti Ortopedici Rizzoli, Bologna, Italy. The expression of tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) and TRAIL receptors was investigated in resting and cytokine-activated purified primary human natural killer (NK) and CD8+ T cells. Resting NK and CD8+ T cells expressed the mRNA for all TRAIL receptors, but TRAIL-R4 was the only receptor clearly detectable on the surface of both cell types. NK cells were activated by interleukin 2 (IL-2) or IL-15, whereas CD8+ T cells were activated by phytohemagglutinin (PHA) + IL-2 followed by IL-2 alone for up to 10 days. On activation, both cell types rapidly expressed TRAIL-R2 and TRAIL-R3, whose expression peaked at day 10 of culture. TRAIL-R1, however, was never expressed at any time point examined, whereas the expression of TRAIL-R4, which showed a progressive increase in CD8+ T cells, remained constant in NK cells. Notwithstanding the expression of TRAIL-R2, recombinant TRAIL did not show any cytotoxic activity on either NK or CD8+ T cells. Both resting and activated NK and CD8+ T cells were found to express high levels of the 2 isoforms of c-FLIP (cellular Fas-associated death domain protein [FADD]–like IL-1–converting enzyme [FLICE]–inhibitory protein). Small interference RNA-mediated inhibition of c-FLIP expression in NK cells abrogated their resistance to the apoptotic effect of soluble TRAIL. Thus, once activated the major cytotoxic effector cells are potentially sensitive to TRAIL but are physiologically protected from its apoptotic action by intracellular level of c-FLIP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Killer cells protect themselves Michael Bennett Blood 2004 104: 2214. [Full Text] [PDF] This article has been cited by other articles: G. Gobbi, P. Mirandola, C. Carubbi, C. Micheloni, C. Malinverno, P. Lunghi, A. Bonati, and M. Vitale Phorbol ester-induced PKC{epsilon} down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation Blood, March 26, 2009; 113(13): 3080 - 3087. [Abstract] [Full Text] [PDF] B. Berent-Maoz, A. M. Piliponsky, I. Daigle, H.-U. Simon, and F. Levi-Schaffer Human Mast Cells Undergo TRAIL-Induced Apoptosis J. Immunol., February 15, 2006; 176(4): 2272 - 2278. [Abstract] [Full Text] [PDF] K. Sato, A. Niessner, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque J. Exp. Med., January 23, 2006; 203(1): 239 - 250. [Abstract] [Full Text] [PDF] N Arbour, E Rastikerdar, E McCrea, Y Lapierre, J Dorr, A Bar-Or, and J P Antel Upregulation of TRAIL expression on human T lymphocytes by interferon b and glatiramer acetate Multiple Sclerosis, December 1, 2005; 11(6): 652 - 657. [Abstract] [PDF] S. Skov, M. T. Pedersen, L. Andresen, P. Thor Straten, A. Woetmann, and N. Odum Cancer Cells Become Susceptible to Natural Killer Cell Killing after Exposure to Histone Deacetylase Inhibitors Due to Glycogen Synthase Kinase-3-Dependent Expression of MHC Class I-Related Chain A and B Cancer Res., December 1, 2005; 65(23): 11136 - 11145. [Abstract] [Full Text] [PDF]

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